Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine

Mitchell J Bartlett; Carolyn J Stopera; Stephen L Cowen; Scott J Sherman; Torsten Falk

doi:10.1016/j.neulet.2025.138114

Differential effects of statins on the anti-dyskinetic activity of sub-anesthetic ketamine

Neurosci Lett. 2025 Jan 4:138114. doi: 10.1016/j.neulet.2025.138114. Online ahead of print.

Authors

Mitchell J Bartlett¹, Carolyn J Stopera², Stephen L Cowen³, Scott J Sherman⁴, Torsten Falk⁵

Affiliations

¹ Department of Neurology, The University of Arizona, Tucson, AZ 85724, USA; Department of Surgery, The University of Arizona, Tucson, AZ 85724, USA; Department of Neurosurgery, The University of Arizona, Tucson, AZ 85724, USA. Electronic address: [email protected].
² Graduate Interdisciplinary Program in Neuroscience, The University of Arizona, Tucson, AZ 85724, USA. Electronic address: [email protected].
³ Department of Psychology, The University of Arizona, Tucson, AZ 85721, USA. Electronic address: [email protected].
⁴ Department of Neurology, The University of Arizona, Tucson, AZ 85724, USA. Electronic address: [email protected].
⁵ Department of Neurology, The University of Arizona, Tucson, AZ 85724, USA; Graduate Interdisciplinary Program in Neuroscience, The University of Arizona, Tucson, AZ 85724, USA; Department of Pharmacology, The University of Arizona, Tucson, AZ 85724, USA. Electronic address: [email protected].

PMID: 39761720
DOI: 10.1016/j.neulet.2025.138114

Abstract

Sub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson's disease (PD) case reports. In this study, we examined the effects on LID of two different statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard model for preclinical LID studies. Ketamine attenuated the development of AIMs, while the non-polar lovastatin only showed anti-dyskinetic activity early in the priming period but did not prevent the development of LID, and the polar pravastatin showed no anti-dyskinetic activity. Furthermore, our main result is that pravastatin blocked the long-term neuroplastic anti-dyskinetic effects of ketamine, while lovastatin did not. This study shows two different statins affect LID and the anti-dyskinetic activity of ketamine differentially, pointing to an important drug interaction. The results further inform and support ongoing clinical testing of sub-anesthetic ketamine to treat LID in individuals with PD.